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THE BULLETIN
decline,” says Buffalo. “And it only requires a laptop camera.” Fast-
forward to 2016, when Buffalo is cofounder of a company called
Neurotrack, which has developed a five-minute computer-based
visual test for memory impairment in humans called Imprint™.
If Neurotrack succeeds in bringing Imprint into doctor’s offices,
the test would serve as a quick, easy, and affordable way to detect
the very earliest manifestations of dementia. A potentially revo-
lutionary tool, Imprint could allow patients to receive a person-
alized risk assessment in the doctor’s office, empowering him or
her to pursue promising lifestyle strategies to maintain cognitive
function or a new therapeutic.
Along with plans to make Imprint available for routine clinical
use, Buffalo hopes to collaborate with ADRC. She thinks the
app can serve as a tool to validate the results of ongoing brain
imaging studies or clinical trials by helping researchers correlate
measurements of memory with other biomarkers in spinal fluid,
blood, or brain images.
In one of these studies, ADRC Director Dr. Tom Grabowski and
Tara Madhyastha, a Research Assistant Professor in the Department
of Radiology, are using functional magnetic resonance imaging
(fMRI) to study the brain network connectivity in ADRC research
participants. They want to establish what Madhyastha calls the
holy grail of neurodegenerative research—whether fMRI scans
can detect and track disease in individuals, and whether PET scan
images of brain blood flow replicate and confirm fMRI results.
If so, the field would be a step closer to using one brain scan to
monitor the effectiveness of a drug in a clinical trial.
Messages in our genes
The UW’s ADRC, one of the country’s top NIH-sponsored centers
for Alzheimer’s research, recently shifted its focus to precision
medicine. Endorsed as President Obama’s “moon shot,” this
approach has revolutionized cancer and cystic fibrosis treatment
by tailoring treatment plans to each individual’s unique profile of
biomarkers, especially genetic risk factors.
“A precision medicine approach to Alzheimer’s disease runs about
a decade behind oncology,” says Grabowski, “but we hope that
the ADRC’s 30-year legacy in neurogenetics will lead to more
personalized, effective treatments for patients.”
From its early days, the ADRC has led the discovery of genetic
causes of Alzheimer’s disease and frontotemporal degeneration
(FTD). Now, Suman Jayadev, Assistant Professor of Neurology
at UW, is harnessing this knowledge with advanced genetic
technology. She leads a project to establish the role of exome
sequencing in clinical decision-making.
The exome is the 2 percent of the 3.2 billion bases of the human
genome that codes for proteins. This small-but-mighty slice of
DNA is the part of the genome that researchers know enough
about to infer the pathological consequences of variations in its
code. So sequencing the exome, rather than the whole genome,
is currently the most practical way to identify the genetic culprits
in many diseases.
Whole exome sequencing is effective in cases of neurodegenera-
tive disease, such as Alzheimer’s and Parkinson’s diseases, ALS,
and frontotemporal degeneration (FTD), because they often have
a genetic basis. About 30 percent of cases carry some genetic
risk factor. As more and more affected families demand informa-
tion about their risks, treatment options, and eligibility for clinical
trials of targeted therapeutics, this technology is gaining a place
in the precision medicine tool chest.
Jayadev, who studies gene mutations in the lab and counsels
people at risk for Alzheimer’s disease, is intimately familiar with
the disconnect between what patients want to know and what
she can tell them. “I’m very interested in how personal exome
RESEARCH AT UW, CONT.
The UW ADRC aims to speed the development of treatments tailored to a person's
genetic risk factors.
Image credit: Ernesto del Aguila III, NHGRI
Graduate student Seth Koenig watches the electrical activity of a neuron in a monkey's
hippocampus.
Photo credit: Beth Buffalo
